tbuckley/cabot-search huggingface dataset:
Twenty-one gene recurrence scores in individuals with breast cancer associated with <i>CHEK2</i> and <i>ATM</i> germline pathogenic variants.
Authors: Payal Deepak Shah, Jamie Brower, Lauren Cuff, Robert Richardville, Jada G. Hamilton, Judy Ellen Garber, Siddhartha Yadav, Fergus Couch, Kenneth Offit, Susan M. Domchek, Mark E. Robson
Journal: Journal of Clinical Oncology (2023)

10585 Background: The 21-gene recurrence score assay (Oncotype DX, Genomic Health Inc., CA) is prognostic, quantifies predicted benefit of adjuvant chemotherapy, and informs clinical decisions for patients with early-stage, hormone receptor-positive (HR+) breast cancer (BC). Differences in Oncotype recurrence scores (RS) in individuals with and without BRCA1 and BRCA2 pathogenic variants (PV) have been demonstrated, but the results of this assay in patients with BC and germline CHEK2 or ATM PV have not previously been described. This is of particular relevance as CHEK2 BC have been associated with a worse prognosis. Methods: Prospective Registry of MultiPlex Testing (PROMPT) is an online research registry for individuals who have had multigene panel testing for inherited cancer susceptibility. We retrospectively evaluated Oncotype DX recurrence scores from PROMPT participants (pts) with PV or likely PV in CHEK2 or ATM. Mood’s median tests were used to compare median RS, and Yates corrected Chi-square tests were used to compare RS distributions between carriers and a genetically unselected reference population. Results: Oncotype DX reports were reviewed for 75 pts with 77 BC (n = 50 pts with CHEK2 PV with 51 BC; n = 24 with ATM PV; n = 1 with CHEK2 and ATM PV with 2 BC). Among CHEK2 carriers, median RS was 17 (range 2-43) overall, 17 (2-36) for pts &lt; age 50, and 18.5 (8-43) for pts ≥age 50 (p-value 0.47), with distributions not significantly different than reference ( &lt; 50, p = 0.70; ≥50, p = 0.93). Ten pts had low penetrance CHEK2 alleles (p.S428F or p.I157T) with median RS 16 (9-28) compared to 18 (2-43) in those with other CHEK2 alleles (p = 0.35). Among ATM carriers, median RS was 17 (1-35) overall, 17 (1-35) for pts &lt; age 50, and 16 (11-32) for pts ≥age 50 (p = 0.51), with distributions also not significantly different ( &lt; 50, p = 0.78; ≥50, p = 0.79). Conclusions: Unlike data seen in BC associated with BRCA1 and BRCA2, Oncotype DX RS in individuals with CHEK2 and ATM-associated BC are similar to the published genetically unselected commercial database median RS of 16, with no clear difference based on penetrance of CHEK2 allele. Proportions of patients &lt; 50 and ≥50 with CHEK2 and ATM PV with RS within the range for chemoendocrine therapy consideration are also similar to the historical reference. The inferior prognosis that has been suggested in CHEK2 BC is not reflected in Oncotype DX RS. [Table: see text]
A phase II clinical trial of chidamide in combination with toripalimab in patients with advanced soft tissue sarcoma.
Authors: Xing Zhang, Ruiqing Peng, Qiuzhong Pan, Bushu Xu, Dongchun Hong, Yi Que
Journal: Journal of Clinical Oncology (2023)

11566 Background: Chidamide is an oral subtype-selective histone deacetylase inhibitor which is effective on the patients with hematological tumors and reported to enhance the efficacy of checkpoint blockade therapies and regulate the host immune response. Here, we report preliminary results of Chidamide in combination with Toripalimab in soft tissue sarcoma (STS) patients. Methods: An open, single arm, phase II study of Chidamide with Toripalimab in patients with advanced soft tissue sarcoma after failure of standard treatment was conducted. Eligible patients could have any number of prior therapies, excluding HDAC inhibitors and immune checkpoint inhibitors treatment. All patients received Chidamide orally at 30mg twice weekly in combination with intravenous Toripalimab 240mg every 21 days until progression or unaccepted toxicity. The primary endpoint was RECIST1.1 objective response rate (ORR). The secondary endpoint included progression free survival (PFS), overall survival (OS), disease control rate(DCR) and safety. Results: Forty-six patients with advanced soft tissue sarcoma were enrolled. The median age of the patients was 47 years and the median prior lines of therapy were 3. The main subtypes included leiomyosarcoma (30.4%), well/dedifferentiated liposarcoma (30%), myxoid/round cell liposarcoma (7%), undifferentiated sarcoma(9%), and osteosarcoma (7%). Treatment was well tolerated with the most common adverse events mainly in grade Ⅰ and grade Ⅱ, including thrombocytopenia (43.5%), nausea(28.3%), neutropenia(23.9%), fatigue (17.4%) and hypothyroidism(15.2%). Among 46 efficacy-evaluable patients, the overall response rate and disease control rate were 23.9% and 80.4%, respectively. The median time to an initial response was 3 months (range, 2 to 14), and the 3-mon and 6-mon progression-free survival rate were 92.7% and 58.9%, respectively. Conclusions: Chidamide with Toripalimab every 21 days was well tolerated and showed promising efficacy in patients with advanced STS. Clinical trial information: NCT04025931 .
Recursive partitioning analysis to identify risk stratification for pediatric rhabdomyosarcoma: A real-world data retrospective cohort study based on the SEER database.
Authors: Zhuangbin Lin, Shuping Qiu, Xiaobo Li, Jianyuan Song, Anchuan Li, Benhua Xu
Journal: Journal of Clinical Oncology (2023)

e22005 Background: For pediatric rhabdomyosarcoma (RMS), IRSG risk stratification is based on two distinct staging systems that differ according to whether surgery is performed. Its complexity hinders its effective clinical application to a certain extent. We aimed to develop a simple, practical, and reproducible risk stratification model to offer treatment guidance for RMS. Methods: We conducted a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database obtained from SEER*Stat software, version 8.4.0. Multivariate Cox regression analysis was used to identify independent prognostic factors in RMS. Later, prognostic factors were integrated to construct an OS prediction nomogram. Recursive partitioning analysis (RPA) was performed to stratify the risk of the patients. Results: A total of 223 patients with pediatric RMS were ultimately included in this study. All patients received chemotherapy, and most received radiotherapy (98.2%). The median follow-up time was 93.0 months, and the overall median survival time was not reached. Multivariate Cox analysis revealed that histology (hazard ratio [HR] = 2.2374, P = 0.031), tumor size (HR = 3.403, P = 0.008), and M classification (HR = 2.060, P = 0.028) were independent factors for OS in RMS. A nomogram was constructed to predict accuracy toward individual OS with a training C-index of 0.698 and a validation C-index of 0.781. Compared to the IRSG risk stratification, the risk groups stratified by RPA allowed for significant distinction between survival curves in our cohort (for 3-y OS, IDI = 0.04454772, P = 0.022; for 5-y OS, IDI = 0.05452665, P = 0.015). Conclusions: The risk stratification model constructed by RPA could help clinicians to identify patients with poor outcomes and assist them in making treatment and surveillance decisions.
Availability of palliative specialty care for adults in community oncology: Results from the 2022 NCORP landscape assessment.
Authors: Tiffany M. Statler, Emily Van Meter Dressler, Carol A Kittel, Melyssa Foust, Kah Poh Loh, Kathryn E. Weaver, Heidi D. Klepin, Chandylen L Nightingale, Jennifer Gabbard
Journal: Journal of Clinical Oncology (2023)

e24125 Background: Palliative care promotes timely symptom management, and care planning and improves quality of life in oncology patients. About 60% of community oncology practices sampled in 2015 had outpatient palliative care. This study updates estimates of palliative care resources in community oncology. Methods: Questions from the 2022 Landscape Assessment of National Cancer Institute Community Oncology Research Program (NCORP) (funding provided by 2UG1CA189824) assessed the availability of specialist palliative care providers and ancillary care services, including utilization of advanced practice providers (APPs). Descriptive statistics describe availability of providers and services. Multivariable logistic regression was used to identify practice characteristics associated with palliative care specialist availability in 2022. Differences in rates of palliative care specialists, outpatient palliative care, APPs and patient portal use between 2015 and 2022 assessment results were assessed using Chi-Square tests, assuming independent time snapshots of general population characteristics. Results: Most community oncology practices sampled in 2015 had palliative care specialists (76%) and 62% of practices reported having outpatient palliative care. Of the 259 non-pediatric exclusive NCORP practice groups included in the 2022 analyses (Table 1), significantly more had palliative care specialists (86%; p = 0.003) and offered palliative care in the outpatient setting (76%; p = 0.001). Most practices utilized APPs (92%) and had a patient portal (95%), while only 41% had a survivorship clinic. Multivariable analyses demonstrated practices with more adult oncology providers (OR = 1.03, p = 0.039) and those with a designated survivorship clinic (OR = 3.16, p = 0.001), were significantly more likely to have specialty palliative care in the outpatient setting. Conclusions: More practices reported availability of palliative care specialists and outpatient services in community oncology practices in 2022 compared to 2015, with more oncology providers being associated with increased odds of having outpatient specialty palliative care in 2022. Smaller community oncology practices with fewer providers may need support to expand their capacity to provide palliative care. [Table: see text]
Yttrium-90 radioembolization for lung cancer metastases: Small institutional experience.
Authors: Iuliia Kovalenko, Wern Lynn Ng, Elham Nasrollahi, Lillian Sangha, Ekaterina Proskuriakova, Yijin Wert, Charles Reninger, Todd Hoffman
Journal: Journal of Clinical Oncology (2023)

e21122 Background: Yttrium-90 radioembolization (Y-90) is a local cancer therapy which can provide quality of life improvement with minimal systemic toxicity. Yet, it remains underused in nonconventional cancers malignancies including lung cancer liver metastases. We present institutional experience in Central PA of treating metastatic liver disease in lung cancer patients. Methods: We performed retrospective analysis of patients with lung cancer liver metastasis who underwent Y90 in a 5-year period at the UPMC Harrisburg. Modified RESIST criteria were used to assess response rates. Common terminology criteria for adverse events v3.0 was used to grade adverse events (AEs). Descriptive statistics were reported including median and range. Results: A total of 7 patients were included in the study with median age of 67. Median time from diagnosis was 13.7 months (5-41), median number of metastases was 3 (1-4), and median number of previous systemic therapies was 1 (1-4). Five patients have received two Y-90 procedures while two patients have received one Y90 procedure. All patients achieved liver partial response with median sustained response of 9.4 months (2-36). A total of 3 patients (42%) developed Grade 1 AEs including rash, abdominal pain, and liver enzymes elevation. Only two patients (28%) developed Grade 3 AEs (liver enzymes elevation). Patient’s characteristics and treatment outcomes are listed in the Table 1. Conclusions: Our institutional experience supports growing body of literature demonstrating safety of Y-90 radioembolization for the treatment of metastatic lung cancer to the liver. Heterogeneity in the individual patient response is multifactorial with further investigation required to understand which patients and at what point in their treatment would benefit from treatment the most. [Table: see text]
Non-vitamin k oral antagonists versus aspirin for primary thromboprophylaxis in patients with multiple myeloma on outpatient chemotherapy: A systematic review and meta-analysis.
Authors: Thomaz Alexandre Costa, Bruno Almeida Costa, Nicole Felix, Amanda Godoi, Alleh Nogueira, Joshua Ryan Richter, Adriana Rossi
Journal: Journal of Clinical Oncology (2023)

e20041 Background: Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased in patients receiving immunomodulatory drugs (IMiDs). Current guidelines suggest that non-vitamin K oral anticoagulants (NOACs) may be an alternative to low-dose aspirin (ASA) for primary thromboprophylaxis in this population. However, there is limited data comparing these two antithrombotic therapies among MM patients undergoing treatment with IMiDs. Methods: We performed a systematic review and meta-analysis to compare NOACs with ASA for primary thromboprophylaxis in individuals with newly-diagnosed or relapsed/refractory MM undergoing outpatient chemotherapy with an IMiD-based regimen. PubMed, Cochrane, and EMBASE were systematically searched from inception to January 2023. Observational studies and randomized controlled trials were included when comparing NOACs versus aspirin for thrombotic and hemorrhagic outcomes. Statistical analysis was performed with Review Manager 5.4.1. Results: We included 10 randomized controlled trials and observational studies comprising 1026 MM patients who underwent primary thromboprophylaxis with NOACs (33%) or ASA (67%). Thromboprophylaxis with NOACs was associated with a significantly lower incidence of VTE compared with ASA (OR, 0.33; 95% CI, 0.16-0.68; p &lt; 0.001; I² = 0%). Each group had one major bleeding event, with no statistically significant difference between NOACs and ASA (OR, 1.35; 95% CI, 0.05-35.51; p = 0.86; I² = 51%). Similarly, clinically relevant non-major bleeding (OR, 0.56; 95% CI, 0.12-2.70; p = 0.47; I² = 0%) and minor bleeding (OR 1.48; 95% CI: 0.42-5.24; p = 0.54; I² = 0%) event rates did not differ significantly between groups. Conclusions: These findings suggest that NOACs may be superior to ASA for VTE prophylaxis among MM patients receiving IMiD-based chemotherapy, with no significant difference in the overall bleeding risk between the two groups.
Redefining early-onset cancer and risk of hereditary cancer predisposition.
Authors: Zsofia Kinga Stadler, Anna Maio, Aliya Khurram, Yelena Kemel, Angelika Padunan, Matilde Borio, Margaret Sheehan, Yonina R. Murciano-Goroff, Michael Francis Walsh, Marie Will, Ying L Liu, Maria Isabel Carlo, Alicia Latham, Julia Lynne Glade Bender, Andrea Cercek, William D. Tap, David B. Solit, Diana Mandelker, Kenneth Offit, Luis A. Diaz
Journal: Journal of Clinical Oncology (2023)

10510 Background: For most solid tumors, early age of onset, a marker for potential increased inherited risk, has been arbitrarily defined as a diagnosis of cancer at age &lt; 50. However, this disregards the variation in mean age of diagnoses across solid tumors resulting in the potential misclassification of patients at increased risk of germline alterations. Methods: 25,305 prospectively ascertained cancer patients, representing 32 solid tumor types, underwent sequencing analysis of up to 90 cancer predisposition genes using next-generation genetic analysis with reporting of germline likely pathogenic (LP) and pathogenic variants (P). Mean age of diagnosis by cancer type, with standard deviations (STD), were calculated according to Surveillance, Epidemiology, and End Results Program (SEER) data. Early-onset (EO-CA), average-onset (AO-CA), and late-onset (LO-CA) cancers were defined as cancers diagnosed &lt; -1 STD, -1 &lt; STD &gt; 1, and &gt; 1 STD around the mean age at diagnosis for the specific cancer type, respectively. Prevalence of LP/P variants was classified according to age of onset. Statistical analyses were performed using STATA. Results: Among 25,305 patients with 32 solid tumor types classified as per SEER data, 31% (n = 7,854) of patients were categorized as having EO-CA. Overall prevalence of germline alterations varied as a function of age at diagnosis with 19.2%(n = 1509), 15.9% (n = 2588/16,299), and 12.9% (149/1152) of EO-CA, AO-CA, and LO-CA patients harboring a germline LP/P variant (p &lt; 0.0001). The enrichment of variants in EO-CAs was driven by high- and moderate-penetrance genes with 13.2%, 9.2% and 5.1% of EO-CA, AO-CA, and LO-CA patients having an LP/P variant (p &lt; 0.0001); low-penetrance germline alterations were static across the age groups (6%, 6.7%, 7.8%). An age cutoff of 50 for early-onset cancer was &gt; 1 STD below the mean age at diagnosis in 20 cancer types resulting in 2,226 patients who would not have been classified as having EO-CA inclusive of 394 patients who tested positive for a germline LP/P, representing 26.1% of all germline EO-CA positives. Conclusions: Early-onset cancer should be defined taking into consideration the mean age at diagnosis for a specific cancer type as an arbitrary cutoff of age &lt; 50 misses over 25% of patients with an inherited cancer predisposition syndrome. Due to the high prevalence of inherited predisposition syndromes, genetic testing of all patients with EO-CA, irrespective of tumor type, is warranted.
Examining the potential for lead-time bias by estimating stage-specific proportions of deaths due to diagnosed cancer.
Authors: Ellen T. Chang, Christina A. Clarke, Graham A. Colditz, Scarlett L. Gomez, Allison W. Kurian, Earl A. Hubbell
Journal: Journal of Clinical Oncology (2023)

10535 Background: Lead-time bias occurs when cancer is detected earlier in time, but with no change in lifespan. Cause of death is not susceptible to lead-time bias; therefore, stratifying cause of death by cancer stage informs the potential for lead-time bias in early detection across cancer types. Methods: Using recent data from 17 US Surveillance, Epidemiology, and End Results (SEER) cancer registries for 1 152 610 first incident primary cancers among patients aged 50–84 years at diagnosis in 2006–2010, we evaluated proportional causes of death by cancer type and uniformly classified stage at diagnosis (American Joint Committee on Cancer, 6th edition), following or extrapolating all patients until death. Results: A minority of cancer patients diagnosed at stages I–II (27%) went on to die from their index cancer, whereas most stage IV cancer patients (85%) did. For patients diagnosed with stage I cancer at all sites combined, an estimated 26% of deaths were due to the index cancer, 61% due to non-cancer causes, and 12% due to a subsequent primary (non-index) cancer. At stage II, 27% of deaths were due to the index cancer, 60% due to non-cancer causes, and 13% due to a non-index cancer. In contrast, at stage IV, 85% of deaths were attributed to the index cancer, with 13% non-cancer and 2% non-index-cancer deaths. Index cancer mortality from stages I–II cancer was proportionally lowest for thyroid, melanoma, uterus, prostate, and breast, and highest for pancreas, liver, esophagus, lung, and stomach. Leading causes of non-index cancer death (lung, pancreas, and colorectal) and non-cancer death (heart disease and COPD) at each stage were similar to those in the general US population. Non-White racial/ethnic groups, including Hispanics and non-Hispanic Blacks, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives, experienced a higher percentage of deaths from stages I–II cancer than non-Hispanic Whites. Conclusions: Across all cancer types, the percentage of patients who went on to die from their cancer was three times greater at stage IV than at stages I–II. As mortality patterns are not influenced by lead-time bias, these data suggest that earlier stage at diagnosis is broadly, if not uniformly, associated with substantially reduced risk of cause-specific death from cancer; therefore, early detection is likely to improve outcomes across cancer types, including those currently unscreened. [Table: see text]
Adjusted indirect treatment comparison of progression-free survival (PFS) associated with DRd and VRd based on MAIA and SWOG S0777 individual patient-level data.
Authors: Brian G. Durie, Shaji Kumar, Eric M. Ammann, Alex Z. Fu, Shuchita Kaila, Annette Lam, Saad Zafar Usmani, Thierry Facon
Journal: Journal of Clinical Oncology (2023)

8037 Background: Both daratumumab in combination with lenalidomide and dexamethasone (DRd) and bortezomib in combination with lenalidomide and dexamethasone (VRd) are endorsed by NCCN guidelines as preferred regimens for the treatment of transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). DRd and VRd have each demonstrated superior efficacy relative to lenalidomide and dexamethasone (Rd) alone in the MAIA and SWOG S0777 trials, respectively, but have not been compared directly in a head-to-head trial. Naive comparisons of efficacy across the 2 trials may be biased because MAIA enrolled only TIE patients (median age 73 years), whereas S0777 enrolled a mixed transplant-not-intended (TNI) population, which included both TIE patients and patients choosing to defer/refuse frontline stem cell transplantation (median age 63 years). Methods: The present study leveraged individual patient-level data (IPD) from both trials to perform an anchored indirect treatment comparison of DRd vs VRd, adjusting for differences in trial eligibility criteria and baseline patient characteristics. Harmonized inclusion criteria (NDMM, age ≥65 years, ECOG performance status ≤2) were applied to both trial populations. Age ≥65 years served as a proxy for TIE status since S0777 enrolled a mixed TNI population. Propensity score (PS) reweighting was used to balance the 2 trial populations on key baseline prognostic factors including age, sex, ISS stage, ECOG performance status, hemoglobin, eGFR, lactate dehydrogenase (LDH) level, and cytogenetic risk. Missing data were addressed with multiple imputation. After alignment of inclusion criteria and PS reweighting, an anchored indirect comparison was performed wherein within-trial progression-free survival (PFS) hazard ratios (HRs) for DRd vs Rd and VRd vs Rd were estimated and used to make indirect inference about PFS for DRd vs VRd. Results: 727 MAIA participants and 198 S0777 participants were eligible for inclusion. After PS reweighting, the trial populations were balanced on the key baseline prognostic factors identified above (standardized difference &lt; 0.1 for each). The adjusted PFS HRs were 0.53 (95% CI: 0.41–0.68; P&lt; 0.0001) for DRd vs Rd in MAIA and 0.88 (0.63–1.23; P= 0.46) for VRd vs Rd in S0777. In the adjusted Rd-anchored indirect comparison, the PFS HR for DRd vs VRd was 0.60 (0.39–0.90; P= 0.02). Conclusions: In this adjusted indirect treatment comparison based on IPD from the MAIA and S0777 trials, PFS was significantly longer for DRd relative to VRd. In the absence of a head-to-head trial comparing DRd and VRd, the present study may help to inform treatment selection in TIE patients with NDMM.